The increased use of laboratory based cellular systems in basic research and pharmaceutical discovery has led to a greater need for in vivo animal studies. As a result, studies have demanded longer time periods for the actual studies which, in turn, leads to higher costs and often results in a disconnect between the in vitro and in vivo data.
Tissue engineering, as introduced in the mid-1980s, has been described as the use of a combination of cells, engineering and materials methods, to improve or replace biological functions. While it was once categorized as a sub-field of biomaterials, it has grown in scope to include suitable biochemical and physiochemical factors to improve or replace biological functions.
Progress in the past decade has enhanced understanding of the structure-function relationships in living organisms. These developments have yielded a set of tissue replacement parts and implementation strategies. Scientific advances in biomaterials, stem cells, biomimetic environments, growth, and differentiation factors have created opportunities to fabricate tissues in the laboratory from combinations of engineered extracellular matrices or scaffolds, cells, and biologically active molecules.
Despite the advances, numerous challenges and fundamental questions remain about how cells work within engineered matrices, thus limiting the utility of the initially designed engineered tissue products. In many cases, creation of functional tissues and biological structures in vitro requires extensive culturing to promote survival, growth and inducement of functionality. In general, cells require maintenance of growth conditions in culture including control of oxygen levels, pH, humidity, temperature, nutrients and osmotic pressure. Tissue engineered cultures, however, present additional problems in maintaining culture conditions. In standard cell culture, diffusion is often the sole means of nutrient and metabolite transport. As a culture grows, such as the case with engineered organs and whole tissues, other mechanisms must be employed to maintain the culture, such as the creation of capillary networks within the tissue.
Another issue with tissue culture is introducing the proper factors or stimuli required to induce functionality. In many cases, simple maintenance culture is not sufficient. Growth factors, hormones, specific metabolites or nutrients, and chemical and physical stimuli are sometimes required. For example, certain cells such as chondrocytes, respond to changes in oxygen tension as part of their normal development. Others, such as endothelial cells, respond to shear stress from fluid flow by blood vessels. Mechanical stimuli, such as pressure pulses seem to benefit various cardiovascular tissues including heart valves, blood vessels, or pericardium.
Further challenges include implementing a more complex functionality in a tissue model, as well as both functional and biomechanical stability in laboratory-gown tissues destined for replacement of tissues needed for animal and human research. As increased costs in clinical research associated with medical care continue to grow exponentially; improved research methods and innovation in tissue engineered modeling will desirably reduce costs while improving deliverable treatment options.